Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis

Nontuberculous mycobacteria are increasingly recognized as important pathogens in peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Mycobacterium gordonae rarely causes human infection and is the least likely mycobacterium to produce clinical infection in CAPD patients. We describe a patient with persistent M. gordonae peritonitis acquired while undergoing CAPD. During 18 months of treatment, clinical improvement occurred but a microbiological cure could not be achieved. Principles of therapy for mycobacterial peritonitis developing during CAPD are reviewed, and potential explanations for our patient's failure to respond to therapy are discussed.     

Host defences in continuous ambulatory peritoneal dialysis and the genesis of peritonitis

Continuous ambulatory peritoneal dialysis (CAPD) has come to be extensively used for the treatment of end-stage renal failure in children, and especially infants, such that now more than half of children on dialysis worldwide receive treatment by this means. Peritonitis, however, is commoner in children than in adults receiving treatment, and is a major source of morbidity and treatment failure in children started on CAPD. Only recently has the immunology of the normal peritoneum been studied extensively, with the need to assess the impact of the installation of large volumes of fluid into the peritoneal sac during dialysis. The main phagocytic defences of the peritoneum depend upon a unique set of macrophages which are present free in the peritoneal fluid but also in the submesothelium and in perivascular collections together with B lymphocytes in the submesothelial area. Both the number of macrophages per unit volume and the concentration of opsonic proteins, such as IgG, complement and fibronectin, are reduced to between only 1% and 5% when dialysis fluid is continuously present in the peritoneal sac. In addition, the fluids used for CAPD are toxic to both macrophages and to mesothelial cells. Thus minor degrees of contamination frequently lead to peritonitis and in addition the majority of patients have catheters inserted in their peritoneum which become colonised with organisms capable of producing exopolysaccharide (slime), which promotes adhesion of the organism to the plastic and protects them against phagocytic attack and the penetration of antibiotics. Thus the peritoneum is in a state of continual inflammation, as well as being a markedly more vulnerable site than the normal peritoneum to the entry of organisms. Whether clinical peritonitis appears in this state of chronic contamination probably depends on perturbation in the balance between host defences and the organism. Whilst Staphylococcus epidermidis is the commonest cause of peritonitis, Staphylococcus aureus and Gram-negative organisms are much more serious and more frequently lead either to temporary catheter removal or discontinuation of dialysis altogether. This review describes the peritoneal defences in relation to the genesis of peritonitis.     

High serum D-lactate in patients on continuous ambulatory peritoneal dialysis

BACKGROUND: As abnormally high serum D-lactate levels may cause neurological impairment, we determined whether patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with lactate-containing fluids have increased serum D-lactate concentrations. METHODS: D- and L-lactate concentrations were determined in peritoneal dialysis fluids and in serum from control subjects (n = 10), haemodialysis patients (n = 10), and CAPD patients (n = 30) before and after 1 h of dialysis. RESULTS: We found the median D-lactate concentration in Dianeal CAPD fluid to be 26 mM (range 19-27), whereas it was less than 0.5 mM in DPCA2 fluid. Control, haemodialysis, and CAPD (DPCA2) patient median serum D-lactate concentrations were below 0.07 mM. However, CAPD (Dianeal) patient serum D-lactate concentrations were 4-fold higher than controls (P < 0.0001), at 0.28 mM, an hour after instillation of D-lactate-containing fluid. Three patients, whose serum D-lactate averaged 0.59 mM, were found to have D-lactate concentrations at 0.22 mM after overnight cessation of dialysis. CONCLUSION: We conclude that CAPD with D-lactate-containing fluids raises serum D-lactate to abnormal levels.     

Outcome of HIV infected patients on continuous ambulatory peritoneal dialysis

A retrospective analysis of 39 HIV infected patients with ESRD cared for in New Haven from 1987 to June 1992 was performed. All patients had evidence for HIV infection at the start of CAPD therapy. Cumulative technique survival at one and two years was 43% and 27%, respectively. Only eight patients transferred to center dialysis. One and two year patient survival on CAPD was 58% and 54%, respectively. Mortality was higher in patients with advanced infection than in those with asymptomatic HIV infection. Hospitalization rates were also higher in patients with advanced infection. HIV infected patients had higher rates of peritonitis (3.9 episodes/outpatient CAPD year) compared to non-HIV infected patients (1.5 episodes/CAPD year), especially for pseudomonal and fungal infections. Active injection drug use and use of the "straight set" system were associated with increased rates of peritonitis. CAPD deserves consideration as a therapy for HIV infected patients with ESRD.     

The pharmacokinetics of once-daily oral 400 mg ofloxacin in patients with peritonitis complicating continuous ambulatory peritoneal dialysis

Seven patients with end-stage renal disease requiring support by continuous ambulatory peritoneal dialysis received once-daily 400 mg oral ofloxacin for 7 days for the treatment of bacterial peritonitis. Serum and peritoneal dialysis fluid (PDF) were collected for assay throughout the course of the study and for 5 days thereafter. Ofloxacin, desmethyl ofloxacin and ofloxacin-N-oxide accumulated over the course of therapy and could still be detected in serum and PDF 5 days after the end of therapy. The mean elimination half-life of ofloxacin in serum was 32 +/- 7 h, desmethyl ofloxacin 45 +/- 26 h and for ofloxacin-N-oxide 44 +/- 15 h. The total mean recovery of ofloxacin and its metabolites from the PDF was 15.4%. This regimen results in serum and PDF concentrations likely to be effective for the treatment of infection for at least 10 days.     

Estimating urea clearance in patients on continuous ambulatory peritoneal dialysis: a multivariate analysis

The purpose of this study was to determine if Kt/V urea in continuous ambulatory peritoneal dialysis (CAPD) could be estimated by a multivariate model based upon simple clinical observations. The study included 439 clearance studies in 301 CAPD patients followed in 8 dialysis centers. Weekly urea clearance, 24 h urine volume and 24 h drain volume were normalized to body water by the formulae of Watson (Kt/V, UV/V and DV/V respectively). Adequate dialysis was defined as Kt/V > or = 2.0 weekly. Subjects at 2 units were used to derive the models, while others were used for model validation. Stepwise multiple linear regression was performed on the derivation set (DS) to identify the clinical variables that correlated with Kt/V. The model was then used to estimate Kt/V for the validation set (VS). In the DS, 110 clearance studies were performed in subjects with residual renal function. Multiple linear regression showed that weekly Kt/V was defined by the expression: Kt/V=1.48 + 24.1 (UV/V) + 2.92(DV/V) - 0.049 (serum creatinine) (r=0.750, p<0.001). In 204 VS studies, the correlation between estimated and measured Kt/V was 0.633. There were marked differences in the proportion of adequately dialyzed patients when Kt/V estimated from the formula shown was <2.0, between 2.0 and 2.3, and >2.3 weekly (7.9%, 54.7% and 79.7%, respectively; p2.3 weekly (8.1%, 68.8%, and 100%, respectively; p<0.001). The risk of low Kt/V can be estimated by multivariate linear models requiring only simple clinical measurements.     

Measuring the economic impact of ambulatory dialysis: the case of continuous ambulatory peritoneal dialysis

BACKGROUND: As concerns the treatment of terminal renal failure (TRF), France is characterized by a minimal use of peritoneal dialysis, even though this technique is as effective and less expensive than others and that authorities precognize to switch patients to out-of-centre techniques, like peritoneal dialysis. The purpose of the article is to estimate benefits for the Social Security induced by an incitative program leading the current structure of TRF treatment to the existing government standards defined in 1984. METHODS: We computed treatment cost differences, on the basis of an incident case of TRF followed during 7 years, between three different situations: the current French structure of TRF treatment (29.5% of patients treated by out-of-center techniques); two reference situations A and B (respectively 45% and 37% of patients treated by out-of-center techniques). We performed a sensitivity analysis on the rate of use of continuous ambulatory peritoneal dialysis (CAPD). We made assumptions on the cost of techniques, the cost of complications and the rate of CAPD treatment failure. RESULTS: Results stress the existence of benefits induced by increased use of out-of-centre techniques on the basis of a 7-year follow-up of an incident TRF patient: around 65,000 FF in situation A with a 20% rate of use of CAPD; around 5,000 FF in situation B with a 15% rate of use of CAPD. Assumptions concerning CAPD treatment lead to an underestimation of the true benefits. CONCLUSION: The study highlights the therapeutic and economic interest to transfer some patients from hemodialysis to peritoneal dialysis.     

A case of peritonitis caused by Roseomonas gilardii in a patient undergoing continuous ambulatory peritoneal dialysis

A case of peritonitis caused by Roseomonas gilardii in a patient receiving continuous ambulatory peritoneal dialysis is presented. The patient's domestic water supply was implicated as the probable source of infection. This is the first report of R. gilardii causing such an infection.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.     

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.     

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.     

Bacteremia complicating peritonitis in peritoneal dialysis patients

Bacteremia is a rare complication of peritonitis in end-stage renal failure (ESRF) patients treated by peritoneal dialysis. Three of our ESRF patients on peritoneal dialysis developed bacteremia during a peritonitis episode (1/19 peritonitis episodes). In 2 cases, the responsible organism was Escherichia coli and peritonitis was most likely associated with infection of the biliary tract. The 3rd patient had a perforation of the colon and Klebsiella spp. was the infective organism. Only the last patient survived but had to be transferred to hemodialysis. Bacteremia during peritonitis is infrequent in peritoneal dialysis patients and it appears to be related to other intra-abdominal events.     

Peritonitis in continuous ambulatory peritoneal dialysis. Culture of peritoneal dialysate fluid

Conventional aerobic and anaerobic culture of peritoneal dialysate effluent from patients in continuous peritoneal dialysis (CAPD) was compared to culture in a semiautomated blood culture system. During a two-year period 78 of 79 consecutive episodes of peritonitis among 45 Danish CAPD patients were cultured and the etiology of the infection found in 73 (94%). The sensitivity of the blood culture system was 88%, whereas the sensitivity of the conventional culture of the dialysate effluent was 81%. This difference is not significant (McNemar test; 0.5 > p > 0.3). The majority of isolates were Gram-positive bacteria dominated by coagulase-negative staphylococci (38%). In comparison, only 2% of the cultures of peritoneal dialysate effluent taken within the same period from patients without clinical signs of peritonitis were positive. All the Gram-positive aerobic bacteria were sensitive to vancomycin whereas 97% of the Gram-negative aerobic bacteria were sensitive to gentamicin. An initial empiric treatment of peritonitis with a combination of vancomycin and gentamicin is recommended.     

Pharmacokinetics of cefdinir and its transfer to dialysate in patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis

Cefdinir (CAS 91832-40-5) was administered orally as a 100-mg capsule (Cefzon) to a total of 12 patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD) to investigate changes in the serum concentrations, excretion rate into the dialysate and serum-protein binding of cefdinir. Cmax values were 1.64-4.34 micrograms/ml, t1/2 values were 10.8-21.9 h., and AUC values were 31.1-73.1 micrograms.h/ml (0-30 h) in four patients given a single oral dose of 100 mg of cefdinir as a capsule. About 1 microgram/ml of cefdinir had still remained in the blood of all the patients 24 h after administration. The serum concentrations of cefdinir were dose-dependent in four patients of each group who were given an oral daily dose of 100 mg for 3 to 8 days and 200 mg (2 capsules) for 4 to 14 consecutive days. No marked change in laboratory test values or clinical symptoms before and after administration were observed in these dose regimes. Protein levels of 5.17-5.71 g/day were eliminated from the peritoneal dialysate and urine. Cefdinir inhibited 90 to 100% of the clinical isolates such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and other enteric bacteria causing catheter infection and peritonitis, and its antibacterial activity was stronger than that of amoxicillin (CAS 26787-78-0) or cefaclor (CAS 53944-73-3) against these clinical isolates.